Lisa M. Greene

BACKGROUND: This prospective study was designed to compare the safety, efficacy, cost, and impact on patient outcome of early total enteral nutrition (TEN) vs total parenteral nutrition (TPN) in acute pancreatitis. METHODS: Patients admitted with acute pancreatitis or an acute flare of chronic pancreatitis, characterized by abdominal pain and elevated serum amylase and lipase, were randomized to receive either isocaloric and isonitrogenous TEN (via a nasojejunal feeding tube placed endoscopically) or TPN (via a central or peripheral line) started within 48 hours of admission. RESULTS: Thirty patients were studied over 32 admissions (TEN given on 16 and TPN on 16) for acute pancreatitis. There were no differences on admission in mean age, Ranson criteria, multiple organ failure score (MOF), or APACHE III score between TEN and TPN groups. Although slower to approach goal feeding over the first 72 hours of admission, TEN patients received 71.3% goal calories by day 4 vs 85.2% for TPN patients (not significant). There were no deaths and no differences between groups in serial pain scores, days to normalization of amylase, days to diet by mouth, serum albumin levels, or percent nosocomial infection. However, the mean cost of TPN per patient was over four times greater than that for TEN ($3294 vs $761, respectively, p < .001). Mean serial Ranson criteria, APACHE III, and MOF scores recorded every 2 to 3 days decreased in the TEN group, whereas those in the TPN group increased. Only the difference in the third Ranson criteria (mean 6.3 days after admission) for the TEN and TPN groups (0.5 vs 2.8, respectively) reached statistical significance (p = .002). Stress-induced hyperglycemia was worse in the TPN group, as serum glucose levels increased significantly over the first 5 days of hospitalization (p < .02), whereas those in the TEN group showed no significant change. An exacerbation of pancreatitis, occurring in one TEN patient when the nasojejunal tube was dislodged into the stomach, resolved after placement back in the jejunum. Three patients who became asymptomatic and normalized amylase on TEN flared upon advancing to diet by mouth. CONCLUSIONS: TEN for acute pancreatitis is as safe and effective, but is significantly less costly than TPN. Compared with TPN, TEN may promote more rapid resolution of the toxicity and stress response to pancreatitis. TEN via jejunal feeding should be used preferentially in this disease setting.

High gastric residual volumes (RVs) are a frequent cause for cessation of total enteral nutrition (TEN). This study was designed to determine the RV that indicates intolerance or inadequate gastric emptying and to compare the RV findings in a blinded fashion with those findings obtained on physical examination and radiography. Twenty healthy normal volunteers (HNV), 8 stable patients with gastrostomy tubes (GTP), and 10 critically ill patients (CIP) were evaluated prospectively for 8 hours while receiving TEN. No subjects were clearly intolerant (ie, vomiting, aspiration). Of the total RVs recorded, 13.1% were ≥150 mL in the CIP group, whereas only 2.4% of the RVs were ≥150 mL in the HNV group. None of the RVs in the GTP group were ≥150 mL. Objective scores on physical examination failed to correlate with RV (p =.397), as did objective scores on radiography (p =.742). However, objective scores on physical examination were significantly related to scores on radiography (p =.016). Abnormal physical examination findings were found in 4 out of 11 patients (GTP + CIP) with RVs &lt;100 mL and in 6 out of 7 with RVs ≥100 mL. Abnormal radiographic results were found in 6 out of 11 patients with RVs &lt; 100 mL, in 7 out of 7 patients with RVs ≥100 mL, and in 4 out of 20 HNVs. There was no difference in RVs obtained from the supine or right lateral decubitus positions. Patients with gastrostomy tubes had lower RVs than did those with nasogastric tubes. Patients receiving higher infusion rates had higher RVs. Low RVs did not seem to guarantee tolerance and adequate gut motility because abnormalities still appeared on physical examination and radiography. A single high RV should not cause automatic cessation of TEN because it did occur in some cases in a setting with normal radiographic and physical examination results, where subsequent RVs were shown to decrease. An RV ≥200 mL obtained from a nasogastric tube (or ≥100 mL obtained from a gastrostomy tube) should raise concern about intolerance, but feedings may continue as physical examination, radiographs, and RV are monitored closely. (Journal of Parenteral and Enteral Nutrition 16: 99—105, 1992)

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the β-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. β-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC₅₀= 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel β-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.